3-(3-Octyloxy-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine | 131986-74-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(3-Octyloxy-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine
• 英文别名: 3-(4-octyloxy-1,2,5-thiadiazol-3-yl)-1,2,5,6-tetrahydro-1-methylpyridine；1-Methyl-5-(4-octyloxy-[1,2,5]thiadiazol-3-yl)-1,2,3,6-tetrahydro-pyridine; oxalic acid；3-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-4-octoxy-1,2,5-thiadiazole
• CAS: 131986-74-8
• 化学式: C₁₆H₂₇N₃OS
• 分子量: 309.476
• InChiKey: IVZSSVVWNPQOIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  66.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(3-octyloxy-1,2,5-thiadiazol-4-yl)-1-methylpyridinium iodide 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 3-(3-Octyloxy-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine
  参考文献：
  名称：

  新型功能性M1选择性毒蕈碱激动剂。3-（1,2,5-噻二唑基）-1,2,5,6-四氢-1-甲基吡啶的合成及构效关系。

  摘要：

  一系列新颖的3-（3-取代-1,2,5-噻二唑-4-基）-1,2,5,6-四氢-1-甲基吡啶（取代的TZTP; 5a-1，7a-h，合成了8、9c-n，11、13j），并通过使用[3H]-氧代remorine-M（Oxo-M）和[3H]-哌仑西平（Pz）作为配体测试了中央毒蕈碱胆碱能受体亲和力。在分离的电刺激兔输精管和自发跳动的豚鼠心房上分别测定化合物对药理定义的M1和M2毒蕈碱受体的效力和功效。还测试了所选化合物在分离的豚鼠回肠中的M3活性。C1-8烷氧基-TZTP 5a-1类似物均以低纳摩尔亲和力取代了[3H] -Oxo-M和[3H] -Pz。描述针对Oxo-M结合和针对Pz结合的链长，直链C1-8烷氧基-TZTP（5a-h）衍生物产生U形曲线，其中丁氧基（5d）和（戊氧基）-TZTP（5e）为最佳链长度。在化合物5a-h抑制输精管制剂中的抽搐高度的能力中也看到了该U形曲线。（戊氧基）

  DOI：

  10.1021/jm00090a019

文献信息

• Combination therapy for treatment of psychoses
  申请人：——

  公开号：US20040023951A1

  公开（公告）日：2004-02-05

  The invention provides combination therapy comprising a first component which is a typical antipsychotic or an atypical antipsychotic and a second component which is a muscarinic agonist for the treatment of psychoses and other disorders.

  这项发明提供了一种联合治疗方案，包括一个第一成分，它是典型抗精神病药或非典型抗精神病药，和一个第二成分，它是一种肌动蛋白受体激动剂，用于治疗精神病和其他疾病。
• Method for treating anxiety using a tetrahydropyridine or azabicyclic oxadiazole or thiadiazole compound
  申请人：ELI LILLY AND COMPANY

  公开号：EP0709095A2

  公开（公告）日：1996-05-01

  The present invention provides a method for treating anxiety in humans using heterocyclic compounds as listed in Claim 1.

  本发明提供了一种使用权利要求 1 所列杂环化合物治疗人类焦虑症的方法。
• Method for treating anxiety using a tetrahydropyridine oxadiazole or thiadiazole compound
  申请人：ELI LILLY AND COMPANY

  公开号：EP0709094A2

  公开（公告）日：1996-05-01

  The present invention provides the use of a compound wherein Z1 is oxygen or sulphur; R is hydrogen, halogen, amino, -NHCO-R, C₃₋₇-cycloalkyl, C₄₋₁₀-(cycloalkylalkyl), -Z-C₃₋₇-cycloalkyl optionally substituted with C₁₋₆-alkyl, -Z-C₄₋₁₀-(cycloalkylalkyl), -Z-C₄₋₁₀-(cycloalkenylalkyl), -Z-C₄₋₁₀-(methylenecycloalkyl-alkyl), -NH-R2, -NR2R3, -NH-OR2, phenyl, phenoxy, benzoyl, benzyloxycarbonyl, tetrahydronaphtyl, indenyl, X, R, -ZR, -SOR, -SO₂R, -Z-R-Z³-R³, -Z-R-Z³-R³-Z⁴-R⁴, -Z-RCO-R³, -Z-R-CO₂-R³, Z-R-O₂C-R³, -Z-R-CONH-R³, -Z-R-NHCOR³, -Z-R-X, -Z-R-Z³-X, wherein Z, Z³, and Z⁴ independently are oxygen or sulphur, and R, R³ and R⁴ independently are straight or branched C₁₋₁₅-alkyl, straight or branched C₂₋₁₅-alkenyl, straight or branched C₂₋₁₅-alkynyl, each of which is optionally substituted with halogen(s), -OH, -CN, -CF₃, -SH, -COOH, -NH-R, -NRR³, C₁₋₆alkyl ester, one or two phenyl, phenoxy, benzoyl or benzyloxycarbonyl wherein each aromatic group is optionally substituted with one or two halogen, -CN, C₁₋₄-alkyl or C₁₋₄-alkoxy, and X is a 5 or 6 membered heterocyclic group containing one to four N, O or S atom(s) or a combination thereof, which heterocyclic group is optionally substituted at carbon or nitrogen atom(s) with straight or branched C₁₋₆-alkyl, phenyl, benzyl or pyridine, or a carbon atom in the heterocyclic group together with an oxygen atom form a carbonyl group, or which heterocyclic group is optionally fused with a phenyl group; and R⁵ and R⁶ may be present at any position, including the point of attachment of the thiadiazole or oxadiazole ring, and independently are hydrogen, straight or branched C₁₋₅-alkyl, straight or branched C₂₋₅-alkenyl, straight or branched C₂₋₅-alkynyl, straight or branched C₁₋₁₀-alkoxy, straight or branched C₁₋₅-alkyl substituted with -OH, -OH, halogen, -NH₂ or carboxy; R¹ is hydrogen, straight or branched C₁₋₅-alkyl, straight or branched C₂₋₅-alkenyl or straight or branched C₂₋₅-alkynyl; or a pharmaceutically acceptable salt or solvate thereof; for the manufacture of a medicament for the treatment of anxiety.

  本发明提供了一种化合物的用途 其中 Z1 是氧或硫； R是氢、卤素、氨基、-NHCO-R、C₃₋₇-环烷基、C₄₋₁₀-(环烷基烷基)、-Z-C₃₋₇-环烷基任选被C₁₋₆-烷基取代、-Z-C₄₋₁₀-(环烷基烷基)、-Z-C₄₋₁₀-(环烯基)、-Z-C₄₋₁₀-(亚甲基环烷基)、-NH-R2、-NR2R3、-NH-OR2、苯基、苯氧基、苯甲酰基、苄氧羰基、四氢萘基、茚基、X、R、-ZR、-SOR、-SO₂R、-Z-R-Z³-R³、-Z-R-Z³-R³-Z⁴-R⁴、-Z-RCO-R³、-Z-R-CO₂-R³、Z-R-O₂C-R³、-Z-R-CONH-R³、-Z-R-NHCOR³、-Z-R-X、-Z-R-Z³-X，其中 Z、Z³、和 Z⁴ 独立地为氧或硫，而 R、R³ 和 R⁴ 独立地为直链或支链 C₁₋₁₅-烷基、直链或支链 C₂₋₁₅- 烷基、直链或支链 C₂₋₁₅- 烷炔基、其中每个都可选地被卤素、-OH、-CN、-CF₃、-SH、-COOH、-NH-R、-NRR³、C₁₋₆烷基酯、一个或两个苯基、苯氧基、苯甲酰基或苄氧基取代、苯甲酰基或苄氧羰基，其中每个芳香基团可任选被一个或两个卤素、-CN、C₁₋₄-烷基或 C₁₋₄-烷氧基取代，且 X 是含有 1 至 4 个 N、O 或 S 原子的 5 或 6 位杂环基团、O 或 S 原子或其组合，该杂环基团的碳原子或氮原子可选择被直链或支链 C₁₋₆-烷基、苯基、苄基或吡啶取代，或该杂环基团中的碳原子与氧原子一起形成羰基，或该杂环基团可选择与苯基融合；和 R⁵ 和 R⁶ 可出现在任何位置，包括噻二唑或噁二唑环的连接点，且各自为氢、直链或支链 C₁₋₅-烷基、直链或支链 C₂₋₅- 烷基、直链或支链 C₂₋₅- 烷炔基、直链或支链 C₁₋₁₀-烷氧基、被 -OH、-OH、卤素、-NH₂ 或羧基取代的直链或支链 C₁₋₅ 烷基；R¹ 是氢、直链或支链 C₁₋₅-烷基、直链或支链 C₂₋₅-烯基或直链或支链 C₂₋₅-炔基；或 其药学上可接受的盐或溶液；用于制造治疗焦虑症的药物。
• Identification of side chains on 1,2,5-thiadiazole-azacycles optimal for muscarinic M1 receptor activation
  作者：Per Sauerberg、Lone Jeppesen、Preben H Olesen、Malcolm J Sheardown、Anders Fink-Jensen、Thøger Rasmussen、Karin Rimvall、Harlan E Shannon、Frank P Bymaster、Neil W DeLapp、Dave O Calligaro、John S Ward、Celia A Whitesitt、Christian Thomsen

  DOI：10.1016/s0960-894x(98)00509-5

  日期：1998.10

  Series of analogs to the functional mi selective agonist, xanomeline (hexyloxy-TZTP), were evaluated for their in vitro ml efficacy in cell lines transfected with the human ml receptor. Systematic variation of the side chain and the azacyclic ring led to the discovery of potent muscarinic agonists with robust ml efficacy, ail having the phenylpropargyloxy/thio as the side chain. The most selective compound was the phenylpropargylthio-[3.2.1] endo analog 28, which is a potent and efficacious mi agonist with no m2 activity. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Piperidine compounds and their preparation and use
  申请人：NOVO NORDISK A/S

  公开号：EP0384288B1

  公开（公告）日：1995-05-24